Ependymal Lined Paraventricular Cerebral Cysts; a Report of Three Cases

J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.4.611 on 1 August 1973. Downloaded from

Journial of Neurology, Neurosurgery, and Psychiatry, 1973, 36, 611-617

Ependymal lined paraventricular cerebral cysts; a report of three cases

D. C. BOUCH, I. MITCHELL, AND A. F. J. MALONEY From the Neuropathology Laboratory, Department ofPathology, University of Edinburgh and Milesmark Hospital, Dunfermline

SUMMARY Three cases are reported, each with a benign ependymal-lined cyst which produced clinical signs and symptoms simulating cerebrovascular disease or cerebral neoplasm. The pathological features are described and their histogenesis discussed.

Intracranial cysts lined by ependyma which are embolus with the main pathological features con- large enough to give rise to symptoms are rare. fined to the brain. Virtually all references to ependymal lined cysts BRAIN Macro The brain showed swelling of the in the literature relate to the colloid or para- Protected by copyright. physeal cyst of the third ventricle. right frontal lobe, flattening of the overlying gyri, and shift of the midline structures to the left. Occupy- This communication describes three cases in ing most of the central white matter of the right each of which a large cyst with watery content frontal lobe was a unilocular cyst (Fig. 1) compres- was found in the centrum semi-ovale. In no case sing, but not communicating with, the lateral ventricle could communication with the ventricular system and displacing the anterior corpus striatum down- be demonstrated. All presented with severe neuro- wards. The cyst, which measured 60 x 4-0 cm in logical signs and symptoms. None was diagnosed during life. Two were thought to have a neoplasm and the third was considered to suffer from cerebrovascular disease. As the pathological de- scription will demonstrate, the cysts were non- neoplastic, probably developmental in origin, and should have been amenable to surgery. http://jnnp.bmj.com/

CASE 1 (NP.871) (RIE.33/38) (Dr. A. C. P. Campbell and Dr. I. W. G. Hill) This 64 year old woman presented in January 1938, having experienced headaches and a feeling of pressure on the top of her head for one year. Over the last two months there was a gradual on September 23, 2021 by guest. deterioration of memory and mental faculties with the onset of drowsiness and confusion. Terminally, her condition deteriorated rapidly necessitating her admission to hospital where she became comatose, dying two weeks later. Details of clinical investigations are lacking but she was considered to have sus- FIG. 1. Case 1. Coronal slice of cerebrum at level of tained cerebral optic chiasma showing a large, smooth-surfaced, uni- thrombosis. locular cyst in the white matter of the right frontal Post mortem examination showed that the im- lobe. Note compression and displacement ofthe ventri- mediate cause of death was a massive pulmonary cular system and rotation of the right basal ganglia. 611 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.4.611 on 1 August 1973. Downloaded from

612 D. C. Bouch, L Mitchell, and A. F. J. Maloney

maximum diameter in the coronal plane and contained clear watery fluid, was separated from the right lateral ventricle by white matter 01 cm thick and from the subarachnoid space over the frontal lobe convexity by white matter and cortex 0-8 cm thick. Its wall was smooth and thin. 't The arteries were healthy. SF~~~ Micro The cyst wall was composed of white matter ....a lined on most of its inner aspect by a single layer of +.p low columnar or cubical epithelial cells, some of which were ciliated (Fig. 2) and contained blepharo- * the .. plasts. In one part of the wall, beneath epithelial 4 * *. lining, there was a small collection of tubules and ..... canaliculi lined by similar, but flattened cells (Fig. 3). .. p X The white matter showed minimal gliosis particularly 9. from those areas denuded of epithelium. There was no evidence of haemorrhage, haemosiderin, or neoplasm. COMMENT It was considered that this cyst was

....0 WI simple, lined by ependyma, and probably of developmental origin. Protected by copyright. .,;7. x S~~~~S CASE 2 4 4 (NPA.115/71) This 60 year old woman presented

.- a in April having noticed weakness of her left arm and dragging of her left leg for one year. This later be- FIG. 2. Case 1. Part of cyst wall linied by ciliated came associated with minor left-sided sensory ependyma. H and E, x 325. changes, slurring of speech, increased urinary fre-

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-Ir. el .j'3. V!'. AWL ':. -::..:,...... w FIG. 3. Case 1. Part of cyst wall showing subjacent tubules lined ... # by H and E, V.- -^ ;. flattened ependyma. AL. "O.: ..,. AP" 9-.. x 275. on September 23, 2021 by guest. NVik. . *.. VI5. .IEWrl W.. '... .::. ... V*4ww-OW

. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.4.611 on 1 August 1973. Downloaded from

Ependymal lined paraventricular cerebral cysts; a report of three cases 613

minimal left-sided weakness and also revealed increased tendon reflexes in the left upper limb, a slightly spastic gait, dysarthria, mental slowness, lethargy, and poor concentration. There was no abnormality of the cardiovascular system and the fundi were normal. It was originally thought that she had an intracerebral space-occupying lesion but plain skull radiographs, electroencephalogram, lumbar cerebrospinal fluid, and a cerebral isotope scan were normal. Other system investigations revealed equivocal thyroid function tests; the 48 hour uptake of 131iodine was consistent with, but not diagnostic of, hypothyroidism; the serum protein-bound iodine was normal. By now the only remaining clinical abnormalities were mental slowness andJlethargy and treatment with thyroxin was started. There was marked improvement in her condition. She be- - -1 was home after .". ir, came alert and active and allowed N . '..j two weeks' further observation.

X .. Three days after discharge from hospital, left- sided weakness and headaches recurred. Her con- %,.0. -4, dition rapidly deteriorated and she was readmitted r.,- to hospital 12 hours later in coma. The left limbs were flaccid, the right spastic, and both plantar Protected by copyright. responses were extensor. Both pupils were fixed, FIG. 4. Case 2. Depressed area of cortex (S) in the the right dilated and the left constricted. There was posterior par-t of the right frotital convexity which no papilloedema. Her condition continued to overlay the partially collapsed intracerebral cyst seeni deteriorate and she died 12 hours after readmission. in Fig. 5. The bridging arachnoid mater has been re- Post mortem examination revealed pathological mnoved. x 05. changes in the brain only. quency, and occasional incontinence. Over the last BRAIN Macro The leptomeninges appeared three months intermittent frontal headaches had healthy except for slight brownish discolouration in become a prominent feature along with some diffi- relation to a sunken area of cortex bridged over by culty in recalling recent events. There was no history arachnoid mater and measuring 6-0 x 5 5 cm across of head injury. and 2 0 cm deep located in the right frontoparietal After hospital admission examination confirmed region close to the falx (Fig. 4). It appeared to have http://jnnp.bmj.com/

FIG. 5. Case 2. Coronal slice of cerebrum showinig the partially collapsed on September 23, 2021 by guest. O intracerebral cyst (C) and overlying lepressed cortex (S). x 0 7. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.4.611 on 1 August 1973. Downloaded from

614 D. C. Bouchl, L Mitchlell, and A. F. J. Maloney

W,0 . j,W.So > ; } ^ ,tS*::APrfit FIG. 6. Case 2. Part of cyst wall with layer of collagen *S re §lAw' s' iz *:_f t ' 2 interposed between flattened *_ * *s vS; SS§|iFet - 8tts~~~~~4 ependyma and slightly gliotic white matter. H and E, x 300.

.7- W ' +'4

resulted from collapse of an underlying intracerebral in January 1972 having been essentially well until

cyst, a tiny opening being seen in the floor through seven months before when she began to feel lost andProtected by copyright. which clear fluid issued. Section of the brain showed confused. After an initial slight improvement her a large, partially collapsed unilocular cyst situated condition deteriorated with the development of in the white matter of the supramedial quadrant of headaches and a right hemiparesis. Later, increasing the posterior aspect of the right frontal lobe (Fig. 5). drowsiness and a Parkinsonian type of tremor of This cyst communicated with the subarachnoid space the right limbs became apparent. via the small opening already noted in the cortex On admission to hospital, examination showed but nowhere did it communicate with the ventricular that her hemiparesis was accompanied by minor system. The cyst measured 6 0 x 4-0 cm in the coronal sensory deficits and there was a right homonymous plane at the level of the mamillary bodies and had a hemianopia. Lumbar cerebrospinal fluid and plain thin wall with a smooth glistening lining. The ventri- radiographs of the skull and chest were normal. cular system was compressed and displaced from An electroencephalogram indicated a left cerebral right to left with the right basal ganglia rotated space-occupying mass which appeared to be lying downwards and laterally. The cyst had extended into in the posterior frontal region. the convolutional white matter and, bounded by Craniotomy and careful needling of the left cortex, had crossed the midline under the falx. posterior frontal region failed to identify any lesion.

The arteries were healthy. She failed to recover consciousness after operation http://jnnp.bmj.com/ and gradually became comatose, remaining so until Micro The wall of the cyst was lined internally her death two weeks later. by an incomplete single layer of non-ciliated, Post mortem examination showed that death was flattened, or cubical epithelial cells lying upon the result of brain swelling and pulmonary oedema. slightly gliotic white matter. Blepharoplasts were not The major pathological lesions were in the brain. identified with certainty. In one area an additional thin layer of acellular collagen was interposed (Fig. 6). BRAIN Macro Operative needle tracks were present There was no evidence of haemorrhage, haemo- in was swel- the left frontal lobe. There generalized on September 23, 2021 by guest. siderin, or tumour. ling of both cerebral hemispheres, particularly the COMMENT This cyst resembles that described in left, with associated uncal herniation and shift of case 1 but has partially collapsed after rupture midline structures to the right. Occupying most of into the subarachnoid space through attenuated the white matter of the posterior half of the left cerebral hemisphere was a large unilocular cyst cortex. It is uncertain when the wall ruptured. measuring 4.0 x 3.0 cm in maximum diameter in the coronal plane (Fig. 7). This cyst had compressed the CASE 3 left lateral ventricle and was separated from it by a (NPA.23/72) This 52 year old woman presented layer of translucent white matter which was stretched J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.4.611 on 1 August 1973. Downloaded from

Ependymal lined paraventricular cerebral cysts; a report of three cases 615

FIG. 7. Case 3. Coronal slice of cerebrum with unilocular cyst (C) in white matter of left hemisphere. x 0-7. Protected by copyright.

FIG. 8. Case 3. Part of cyst etb wall lined by ciliated ependyma E~~-.J~ fl~~~~~~~~~~~~~~~~~~~~~~~~A lying upon normal white matter. H and E, x 700.

N+4M;t < is; IW W s http://jnnp.bmj.com/ ¼ K i z< ;St

to 0.1 cm in thickness and from the subarachnoid COMMENT This case is virtually identical with space by white mattert% and§cortex . .thinned |; to4 0.5~~~~,cm case 1. in the parasagittal area of the left parietal lobe. The arteries were free from disease. on September 23, 2021 by guest. DISCUSSION Micro The cyst wall was formed of white matter In each of the three cases described a large unilo- lined internally by a single layer of epithelial cells the white some of which were columnar cular cyst was located entirely within i~~~~~~~~~~and ciliated (Fig. 8) matter of one cerebral hemisphere close to, but and contained blepharoplasts, while others were low, cubical, or flattened. In areas the epithelial not communicating with, the adjacent lateral lining was lost and there was minimal gliosis. There ventricle. was no evidence of tumour, haemorrhage or haemo- In cases 1 and 3 the cysts were lined in some siderin. places by tall columnar, ciliated epithelium con- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.4.611 on 1 August 1973. Downloaded from

616 D. C. Bouch, L Mitchell, and A. F. J. Maloney taining blepharoplasts indistinguishable from of histological details, no final decision can be ependyma. In case 2 the epithelium was essen- reached. tially similar, with the exception that cilia were Porencephaly was originally described by not identified. Nevertheless, we consider on Heschl (1859) as a defect in the cerebrum allow- morphological grounds that all three cysts were ing communication between the ventricular lined by ependyma. system and the subarachnoid space. The meaning There are few references to ependymal-lined of the term porencephaly has been modified to cysts in the literature and the majority of these include almost any type of cerebral cyst, not are concerned with the colloid cyst of the third obviously secondarily acquired whether or not it ventricle (Kolin, 1970; Sakata Yamada, Hoshino, communicates with the ventricular system, the Imamura, Matsui, and Takahashi, 1970). Only subarachnoid space, or both. The application of Jakubiak, Dunsmore, and Beckett (1968) and such terms as pseudoporencephaly and closed Argyopoulos and Heppner (1970) have described porencephaly have merely added to the con- histologically proven, ependymal-lined cysts fusion. We think that Heschl's original descrip- morphologically similar to those found in our tion should be retained and therefore do not cases. A recent paper by Harrison (1971) de- consider any of the cysts in our cases to be ex- scribes 14 cases of hydrocephalus in children, amples of true porencephaly. Although in case 2 which were associated with arachnoid cysts; five the cyst did communicate with the subarachnoid of these were lined by ependyma. Jakubiak et al. space, we believe this followed rupture of its (1968) reported four cases of supratentorial brain attenuated wall. Jakubiak et al. (1968) considered that the cysts: two were lined by ependyma; one of these Protected by copyright. lay within the white matter ofthe left frontal lobe ependymal-lined cysts in their two cases arose and did not communicate with the ventricular during embryological development of the brain, system or the subarachnoid space, the other was being 'developmental defects in which there is a situated in the subarachnoid space over the left disorder in the formation of the mantle layer parietal lobe and did not communicate with the leading to displacement ofthe ependyma into the ventricular system; the remaining two cases were subarachnoid space. Isolated and pinched-off described as arachnoid cysts and were lined by immature lining cells give origin to these cysts'. fibrous tissue. Argyopoulos and Heppner (1970) In support of this view they emphasized that: (1) described a single case of an ependymal-lined the cysts were lined in part by ciliated ependyma cyst within the white matter ofthe right temporo- and they contended that ciliated ependyma is parietal region. It did not communicate with the only found in the ventricles of normal, new- ventricular system or the subarachnoid space; born, or foetal brains; (2) the indentations, in- there were also several similar but smaller associ- clusion cysts, and diverticula lined by similar, but ated cysts. sometimes flattened, epithelium found close to the cyst walls, may represent immature choroid http://jnnp.bmj.com/ Benign intracerebral cysts have been described plexus; (3) groups of ependymal cells and small in previous papers; the majority ofthe cysts were ependymal-lined canals are often found close to considered to be examples of porencephaly the occipital horns of normal lateral ventricles. (Pendergrass and Perryman, 1946; Drew and Russell (1950), however, states that cilia may Grant, 1948) with a much smaller number either persist on the ventricular ependyma into adult not thought to be porencephalic (Handa and life, an observation that we have confirmed, so Bucy, 1956) or not classified (Miller, 1952). These that the mere presence of ciliated epithelium in on September 23, 2021 by guest. reports were mainly concerned with diagnosis and the cyst wall does not alone support a develop- treatment; little attention was paid to the actual mental origin. Of greater import is the fact that structure ofthe cysts and the histological appear- ependyma does not regenerate after being ances were not described. damaged or lost from a previously normal From a study of the macroscopical reports the ventricular wall as a result of hydrocephalus single case described by Miller and two of the (Russell, 1949). It would therefore seem improb- three cases described by Handa and Bucy seem able that a secondarily acquired cystic lesion in to resemble our cases closely, but in the absence white matter could acquire de novo an ependy- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.4.611 on 1 August 1973. Downloaded from

Ependymal linedparaventricular cerebral cysts; a report of three cases 617

mal lining, ciliated or non-ciliated, especially if the lengthy history may indeed suggest the pres- the cyst did not communicate with the ventricle ence of cerebrovascular disease in the middle- in any way. For this reason, and in view of the aged subject. When evidence of raised intra- absence of tumour, haemorrhage, or significant cranial pressure is found and a space-occupying gliosis from the cyst walls, we consider that in lesion detected by special techniques, a diagnosis each of the three cases now presented the cyst of neoplasm will almost certainly be made unless was of developmental origin. the cyst is entered accidentally during ventriculo- Ependymal-lined tubules, similar to those de- graphy (Handa and Bucy 1956). A firm diagnosis scribed by Jakubiak et al. were found in case 1 can be made only at operation with the help of close to the cyst wall but these we consider to be histological examination of the cyst wall. extensions. It is of interest that clinical features Treatment by establishing drainage of the did not develop until late in life. It is not possible cyst into the subarachnoid space (Jakubiak et to state how large the cysts were during the latent al., 1968), or into the ventricular system (Argyo- period or what caused them to increase in size. poulos and Heppner, 1970) appears to lead to Ependyma was so readily found in sections taken complete cure. from widely separated areas of the wall in each case that the cysts, while still symptomless, must We wish to thank our clinical colleagues for their co- presumably have been of an appreciable size. operation; Dr. J. G. Begg for performing the No trace of choroid plexus was found in any of necropsy on case 2; Mr. James Paul of the Depart- the cysts. Unfortunately, the fluid was not ex- ment of Medical Photography for the photographs; and our technicians under the guidance of Mr. J.

amined biochemically. Jakubiak et al. (1968) Protected by copyright. reported that the protein content of the cyst fluid Masson for the histological sections. in one of their cases was 14 times greater than the protein content of the cerebrospinal fluid REFERENCES and suggested that such a level of protein would Argyopoulos, G., and Heppner, F. (1970). Angeborene tend to draw in fluid from the surrounding tis- Ependymzysten. Zentrablatt fur Neurochirurgie, 31, 39-41. Drew, J. H., and Grant F. C. (1948). Benign cysts ofthe brain. sues and cause enlargement of the cysts. They An analysis with comparison of results of operative and postulated a direct secretory activity for the non-operative treatment in thirty cases. Journal of Neuro- lining of ependymal cells but this does not ex- surgery, 5, 107-123. Handa, H., and Bucy, P. C. (1956). Benign cysts of the brain plain why the protein secretion should apparently simulating brain tumor. Journal of Neurosurgery, 13, 489- have been delayed for many years. The finding 499. Harrison, M. J. G. (1971). Cerebral arachnoid cysts in of an incomplete ependymal lining upon slightly children. Journal of Neurology, Neurosurgery, and Psy- gliotic white matter in each of our cases is chiatry, 34, 316-323. reminiscent of the histological appearance of Heschl, R. (1859). Gehirndefect und Hydrocephalus. Vierteljahrschrift fur praktische Heilkunde, 61, 59-74. the ventricular wall in hydrocephalus. The aver- Jakubiak, P., Dunsmore, R. H., and Beckett, R. S. (1968). age clinical history was about one year and if Supratentorial brain cysts. Journal of Neurosurgery, 28, http://jnnp.bmj.com/ the intermittent nature of the symptoms was due 129-136. Kolin, V. (1963). Eine ependymzyste im foramen interventri- to the cysts periodically enlarging and causing culare monroi. Zentralblatt fur allgemeine Pathologie und rupture of parts of their ependymal lining, thus Pathologische Anatomie, 104, 552-664. Miller, D. (1952). Cyst of a cerebral hemisphere treated by exciting a mild gliosis, the ultimate appearance intraventricular drainage. Journal ofNeurosurgery, 9, 219- of the cysts is readily explained. A slightly 221. higher intracystic pressure in case 2 would ac- Pendergrass, E. P., and Perryman, C. R. (1946). Poren- cephaly. American Jouirnal of Roentgenology, 56, 441-463. count for the flattening of the ependymal lining Russell, D. S. (1949). Observations on the Pathology of on September 23, 2021 by guest. cells and the rupture of the attenuated wall into Hydrocephalus, p. 119. Medical Research Council Special the subarachnoid space. Report Series No. 265. H.M.S.O: London. Russell, D. S. (1950). The pathology of intracranial tumours. The clinical history and examination and Postgraduate Medical Journal, 26, 109-125. results of other investigations are not diagnostic Sakata, K., Yamada, H., Hoshino, M., Imamura, T., Matsui, J., and Takahashi, C. (1970). Ependymal cyst of the third of the presence of a benign intracerebral cyst. ventricle. Report of a case and review of the literature. The intermittent nature of the symptoms and Brain and Nerve, 22, 1325-1352.